A Phase I/II Clinical Trial of Intradermal, Controllable Self-Replicating Ribonucleic Acid Vaccine EXG-5003 against SARS-CoV-2

Takenao Koseki, Mayumi Teramachi, Minako Koga, Minoru S.H. Ko, Tomokazu Amano, Hong Yu, Misa Amano, Erica Leyder, Maria Badiola, Priyanka Ray, Jiyoung Kim, Akihiro C. Ko, Achouak Achour, Nan Ping Weng, Takumi Imai, Hisako Yoshida, Satsuki Taniuchi, Ayumi Shintani, Hidetsugu Fujigaki, Masashi KondoYohei Doi

Research output: Contribution to journalArticlepeer-review

Abstract

mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have played a key role in reducing morbidity and mortality from coronavirus disease 2019 (COVID-19). We conducted a double-blind, placebo-controlled phase I/II trial to evaluate the safety, tolerability, and immunogenicity of EXG-5003, a two-dose, controllable self-replicating RNA vaccine against SARS-CoV-2. EXG-5003 encodes the receptor binding domain (RBD) of SARS-CoV-2 and was administered intradermally without lipid nanoparticles (LNPs). The participants were followed for 12 months. Forty healthy participants were enrolled in Cohort 1 (5 µg per dose, n = 16; placebo, n = 4) and Cohort 2 (25 µg per dose, n = 16; placebo, n = 4). No safety concerns were observed with EXG-5003 administration. SARS-CoV-2 RBD antibody titers and neutralizing antibody titers were not elevated in either cohort. Elicitation of antigen-specific cellular immunity was observed in the EXG-5003 recipients in Cohort 2. At the 12-month follow-up, participants who had received an approved mRNA vaccine (BNT162b2 or mRNA-1273) >1 month after receiving the second dose of EXG-5003 showed higher cellular responses compared with equivalently vaccinated participants in the placebo group. The findings suggest a priming effect of EXG-5003 on the long-term cellular immunity of approved SARS-CoV-2 mRNA vaccines.

Original languageEnglish
Article number1767
JournalVaccines
Volume11
Issue number12
DOIs
Publication statusPublished - 12-2023

All Science Journal Classification (ASJC) codes

  • Immunology
  • Pharmacology
  • Drug Discovery
  • Infectious Diseases
  • Pharmacology (medical)

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